Plasmapheresis is a process of separatihg plasma from whole blood. The plasma-depleted blood is comprised principally of cellular components, i.e., red blood cells, white blood cells and platelets. Plasma is comprised largely of water, but also contains proteins and various other noncellular compounds, both organic and inorganic.
Continuous plasmapheresis is a process of continuously removing whole blood from a subject, separating plasma from the blood and returning the plasma-depleted blood to the subject in a continuous extracorporeal circuit.
Plasmapheresis is currently used to obtain plasma for various transfusion needs, for preparation of fresh-frozen plasma, for subsequent fractionation to obtain specific proteins such as serum albumin, to produce cell culture media, and for disease therapies involving either the replacement of plasma or removal of specific disease-contributing factors from the plasma.
Plasmapheresis can be carried out by centrifugation or by filtration. Generally, in known filtration apparatus, whole blood is conducted in a laminar flow path across one surface, i.e., the blood side surface, of a micro-porous membrane filter. Useful micro-porous membrane filters have pores which substantially retain the cellular components of blood but allow plasma to pass through. Such pores are referred to herein as cell-retaining pores. Typically, cell-retaining pore diameters are 0.1 .mu.m to 1.0 .mu.m.
Various filtration devices for plasmapheresis are disclosed in the literature. U.S. Pat. No. 3,705,100 discloses a center-fed circular membrane having a spiral flow path. U.S. Pat. No. 4,212,743 discloses a device having divergent flow channels. German Patent No. 2,925,143 discloses a filtration apparatus having parallel blood flow paths on one side of a membrane and parallel plasma flow paths, which are perpendicular to the blood flow paths, on the opposite surface of the membrane. U.K. Patent Application No. 2,037,614 discloses a rectilinear double-membrane envelope in which the membranes are sealed together at the ends of the blood flow path. U.K. Patent Specification No. 1,555,389 discloses a circular, center-fed, double-membrane envelope in which the membranes are sealed around their peripheries. German Patent No. 2,653,875 discloses a circular, center-fed double-membrane device in which blood flows through slot-shaped filter chambers.
During plasmapheresis, it is desirable to attain high plasma separation efficiency. High plasma separation efficiency means that a large percentage of available plasma is removed. Membrane fouling, however, may impede maintenance of high separation efficiency for an extended period of time. Membrane fouling is discussed in Asanuma, Y., et al., Proc. Euro. Soc. Artif. Organs 6: 308, 1979 and Folstrom, R. J., et. al., Trans. Am. Soc. Artif. Organs 21: 602, 1975. It is believed to be a response to convective forces depositing components of the blood on the membrane. As fouling progresses, plasma flow will decline or can be maintained by increasing the difference in pressure between the blood side and plasma side of the membrane, i.e., transmembrane pressure difference. High transmembrane pressure difference may cause undesirable molecular scale sieving and blood trauma.
It is an object of this invention to provide a method for plasmapheresis by filtration which can be carried out with high plasma separation efficiency for long periods of time by passing plasma through a membrane in an efficient manner, and apparatus therefor.